Tolerance to the bronchoprotective effect of salmeterol 12 hours after starting twice daily treatment.
BACKGROUND
Regular use of salmeterol has been associated with reduced bronchoprotective effect against methacholine as early as 24 hours after initiating treatment.


OBJECTIVE
To determine whether loss of the bronchoprotective effect measured one hour after salmeterol could be demonstrated 12 hours following one previous dose.


METHODS
Ten subjects with stable, mild asthma were enrolled in a randomized, placebo-controlled, double-blind, crossover study comparing two 2-dose treatment periods: (1) blinded salmeterol 50 microg inhaled at bedtime, followed by unblinded salmeterol 50 microg inhaled 12 hours later and (2) blinded placebo inhaled at bedtime, followed by unblinded salmeterol 50 microg inhaled 12 hours later. The methacholine PC20 was measured one hour after the morning salmeterol; FEV1 was measured just prior to the morning salmeterol dose and at the start of the methacholine inhalation test.


RESULTS
The mean log methacholine PC20 recorded one hour after a single dose of salmeterol (1.20 +/- 0.17 SE) was significantly higher than the mean log methacholine PC20 recorded after two doses of salmeterol at 12-hour intervals (1.00 +/- 0.16 SE; P = .024). The mean FEV1 12 hours after salmeterol was significantly higher than the mean FEV1 recorded 12 hours after placebo (P = .0017), however, there was no significant difference between the FEV1 recordings one hour after the two unblinded doses of salmeterol.


CONCLUSIONS
Tolerance to the bronchoprotective effect of salmeterol against methacholine induced bronchoconstriction occurs extremely quickly as it is evident 12 hours after starting twice daily treatment.
Drotar
D E
DE
Department of Medicine, Royal University Hospital, Saskatoon, Canada.
Davis
E E
EE
Cockcroft
D W
DW
D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D000068299:Salmeterol Xinafoate
D000319:Adrenergic beta-Antagonists; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate; D000420:Albuterol